Marina Bortul

In vivo dosimetry and shielding disk alignment verification by EBT3 GAFCHROMIC film in breast IOERT treatment

Intraoperative electron radiation therapy (IOERT) cannot usually benefit, as conventional external radiotherapy, from software systems of treatment planning based on computed tomography and from common dose verify procedures. For this reason, in vivo film dosimetry (IVFD) proves to be an effective methodology to evaluate the actual radiation dose delivered to the target. A practical method for IVFD during breast IOERT was carried out to improve information on the dose actually delivered to the tumor target and on the alignment of the shielding disk with respect to the electron beam. Two EBT3 GAFCHROMIC films have been positioned on the two sides of the shielding disk in order to obtain the dose maps at the target and beyond the disk. Moreover the postprocessing analysis of the dose distribution measured on the films provides a quantitative estimate of the misalignment between the collimator and the disk. EBT3 radiochromic films have been demonstrated to be suitable dosimeters for IVD due to their linear dose‐optical density response in a narrow range around the prescribed dose, as well as their capability to be fixed to the shielding disk without giving any distortion in the dose distribution. Off‐line analysis of the radiochromic film allowed absolute dose measurements and this is indeed a very important verification of the correct exposure to the target organ, as well as an estimate of the dose to the healthy tissue underlying the shielding. These dose maps allow surgeons and radiation oncologists to take advantage of qualitative and quantitative feedback for setting more accurate treatment strategies and further optimized procedures. The proper alignment using elastic bands has improved the absolute dose accuracy and the collimator disk alignment by more than 50%. PACS number: 87.55.khIntraoperative electron radiation therapy (IOERT) cannot usually benefit, as conventional external radiotherapy, from software systems of treatment planning based on computed tomography and from common dose verify procedures. For this reason, in vivo film dosimetry (IVFD) proves to be an effective methodology to evaluate the actual radiation dose delivered to the target. A practical method for IVFD during breast IOERT was carried out to improve information on the dose actually delivered to the tumor target and on the alignment of the shielding disk with respect to the electron beam. Two EBT3 GAFCHROMIC films have been positioned on the two sides of the shielding disk in order to obtain the dose maps at the target and beyond the disk. Moreover the postprocessing analysis of the dose distribution measured on the films provides a quantitative estimate of the misalignment between the collimator and the disk. EBT3 radiochromic films have been demonstrated to be suitable dosimeters for IVD due to their linear dose-optical density response in a narrow range around the prescribed dose, as well as their capability to be fixed to the shielding disk without giving any distortion in the dose distribution. Off-line analysis of the radiochromic film allowed absolute dose measurements and this is indeed a very important verification of the correct exposure to the target organ, as well as an estimate of the dose to the healthy tissue underlying the shielding. These dose maps allow surgeons and radiation oncologists to take advantage of qualitative and quantitative feedback for setting more accurate treatment strategies and further optimized procedures. The proper alignment using elastic bands has improved the absolute dose accuracy and the collimator disk alignment by more than 50%. PACS number: 87.55.kh.

Interval Breast Cancer Versus Screen-Detected Cancer: Comparison of Clinicopathologic Characteristics in a Single-Center Analysis

Background: The introduction of breast screening programs has raised the problem of interval breast cancers (IBC). The aims of this study were to analyze the impact of IBC on the screening program, to compare IBC and screen‐detected cancers (SDC), and to identify possible predictors of mortality. Patients and Methods: Patients with breast cancer diagnosed during the regional breast screening program between January 2008 and December 2013 at a single center in Italy were included. Demographic, preoperative, and postoperative data were prospectively collected and retrospectively analyzed. Results: Five hundred thirty‐four patients were enrolled; 106 women (19.9%) had IBC and 428 women (80.1%) SDC. IBC presented more aggressive features compared to SDC, such as tumor invasiveness (95% vs. 85%; P = .005), tumor size (≥ pT2 37% vs. 21%; P = .001), grade (G3 39% vs. 17%; P < .001), and St Gallen molecular subtype (triple negative 22% vs. 7%; P < .001), resulting in higher distant recurrence rate (8% vs. 2%; P = .009) and worse overall and disease‐free survival (P = .03 and P = .001, respectively). Cox multivariate regression analysis identified St Gallen molecular subtype as the only predictor of mortality in patients with breast cancer (P = .03). Conclusion: IBC accounted for one‐fifth of all breast cancers diagnosed in women who followed the regional screening program. Furthermore, IBC appeared to have more aggressive features compared to SDC, leading to worse survival. These worse survivals depended on St Gallen molecular subtype. Micro‐Abstract: Interval breast cancers (IBC) have been of great concern since breast mammogram screening programs were introduced. We compared IBC to screen‐detected cancers (SDC). IBC accounted for one‐fifth of all breast cancers diagnosed in women who followed the regional screening program. IBC appeared to be more aggressive than SDC in terms of tumor invasiveness, size, and St Gallen molecular subtype, leading to worse overall and disease‐free survival.

Advances in systemic therapy for metastatic breast cancer: future perspectives

Breast cancer (BC) is the most common cancer in women worldwide. One in eight women will develop the disease in her lifetime. Notwithstanding the incredible progress made in this field, BC still represents the second most common cause of cancer-related death in women. Targeted drugs have revolutionised breast cancer treatment and improved the prognosis as well as the life expectancy of millions of women. However, the phenomenon of primary and secondary pharmacological resistance is becoming increasingly evident, limiting the efficacy of these agents and calling for a better in-depth knowledge and understanding of the biology as well as the biochemical crosstalk underlying the disease. The advent of laboratory technologies in the clinical setting such as the routine use of next generation sequencing has allowed identification of new genetic alterations as well as providing a precise picture of the molecular landscapes of each tumour. Consequently, new specific therapeutic approaches are becoming available to minimise or delay the occurrence of resistance. In this review, we analyse the latest research and news from the clinical development side for each BC subtype.

Modifiable and non-modifiable risk factors for surgical site infection after colorectal surgery: a single-center experience

PurposeSurgical site infection (SSI) is the most common complication of colorectal surgery, resulting in significant burden in terms of morbidity and length of hospital stay. The aims of this study were to establish the incidence of SSI in patients undergoing colorectal surgeries and to identify potentially modifiable risk factors to reduce overall SSI rates.MethodsThis retrospective study analyzed patients who underwent colorectal resection at our Department. Patients were identified using a prospective SSI database. Univariate and multivariate analyses were used to identify risk factors.ResultsA total of 687 patients were enrolled in the study and the overall SSI rate was 19.9% (137 patients). Superficial incisional surgical site infections (SSSIs) developed in 52 (7.6%) patients, deep incisional surgical site infections (DSSIs) developed in 15 (2.2%), and organ/space infections (OSIs) developed in 70 (10.1%). Univariate and multivariate analyses confirmed that age, diabetes, emergency surgery, and a high infection risk index are risk factors for SSI.ConclusionsThere are some modifiable and non-modifiable risk factors for SSI. IRI and age are non-modifiable, whereas the timing of surgery and diabetes can be modulated by trying to defer some emergency procedures to elective ones and normalizing the glycemia of diabetic patients.

The prognostic value of PI3K mutational status in breast cancer: A meta-analysis

Breast cancer (BC) is the second most common cause of cancer‐related deaths in women worldwide. The availability of reliable biomarkers of response/resistance to cancer treatments would benefit patients and clinicians allowing for a better selection of BC patients most likely to respond to a specific treatment. Phosphatidylinositol 3‐kinase (PI3K) enzymes are involved in numerous cellular‐ functions and processes. The gene encoding for PI3K catalytic subunit p110α is mutated in 20‐40% of BC. We performed a meta‐analysis of the current literature on randomized clinical trials, investigating the role of PIK3CA mutational status as prognostic factor, and predictor of response to anti‐cancer treatments. Overall 1929 cases were included. The pooled analysis confirmed that the presence of a PIK3CA mutation represents an independent negative prognostic factor (HR = 1.67, 95%CI: 1.15‐2.43; P = 0.007) in BC, as previously reported. As PI3K signaling is also a result of other pathways’ hyperactivation, further investigation of potential biomarkers able to predict likelihood of response to anti‐PI3K/mTOR, anti‐HER2, and other TKRs is warranted in future randomized clinical trials.

Medicine Goes Female: Protocol for Improving Career Options of Females and Working Conditions for Researching Physicians in Clinical Medical Research by Organizational Transformation and Participatory Design

Background All European countries need to increase the number of health professionals in the near future. Most efforts have not brought the expected results so far. The current notion is that this is mainly related to the fact that female physicians will clearly outnumber their male colleagues within a few years in nearly all European countries. Still, women are underrepresented in leadership and research positions throughout Europe. Objectives The MedGoFem project addresses multiple perspectives with the participation of multiple stakeholders. The goal is to facilitate the implementation of Gender Equality Plans (GEP) in university hospitals; thereby, transforming the working conditions for women working as researchers and highly qualified physicians simultaneously. Our proposed innovation, a crosscutting topic in all research and clinical activities, must become an essential part of university hospital strategic concepts. Methods We capture the current status with gender-sensitive demographic data concerning medical staff and conduct Web-based surveys to identify cultural, country-specific, and interdisciplinary factors conducive to women’s academic success. Individual expectations of employees regarding job satisfaction and working conditions will be visualized based on “personal construct theory” through repertory grids. An expert board working out scenarios and a gender topic agenda will identify culture-, nation-, and discipline-specific aspects of gender equality. University hospitals in 7 countries will establish consensus groups, which work on related topics. Hospital management supports the consensus groups, valuates group results, and shares discussion results and suggested measures across groups. Central findings of the consensus groups will be prepared as exemplary case studies for academic teaching on research and work organization, leadership, and management. Results A discussion group on gender equality in academic medicine will be established on an internationally renowned open-research platform. Project results will be published in peer-reviewed journals with high-impact factors. In addition, workshops on gender dimension in research using the principles of Gendered Innovation will be held. Support and consulting services for hospitals will be introduced in order to develop a European consulting service. Conclusions The main impact of the project will be the implementation of innovative GEP tailored to the needs of university hospitals, which will lead to measurable institutional change in gender equality. This will impact the research at university hospitals in general, and will improve career prospects of female researchers in particular. Simultaneously, the gender dimension in medical research as an innovation factor and mandatory topic will be strengthened and integrated in each individual university hospital research activity. Research funding organizations can use the built knowledge to include mandatory topics for funding applications to enforce the use and implementation of GEP in university hospitals.

Cell-free DNA integrity for the monitoring of breast cancer: Future perspectives?

Breast cancer (BC) is the most common cancer and the second cause of death in women worldwide. Therapeutic options are increasing, but the response to treatments is not always efficient and the risk of recurrence covers decades. In this perspective, the need to have a proper follow-up for the therapeutic responses and for anticipating recurrence it is urgent in the clinical setting. Liquid biopsy provides the basic principle for a non-invasive method for the routinely monitoring of BC. However, due to the heterogeneity of tumors during onset and progression, the search for tumor DNA mutations of targeted genes in plasma/serum is a limiting factor. A possible approach overtaking this problem comes from the measurement of cell-free DNA integrity, which is an independent factor from the mutational status and theoretically is representative of all tumors. This review summarizes the state-of-the-art of cell-free DNA integrity researches in BC, the controversies and the future perspective.

FMECA Application to Intraoperative Electron Beam Radiotherapy Procedure As a Quality Method to Prevent and Reduce Patient’s Risk in Conservative Surgery for Breast Cancer

Introduction Failure Mode Effects and Criticalities Analysis (FMECA) represents a prospective method for risk assessment in complex medical practices. Our objective was to describe the application of FMECA approach to intraoperative electron beam radiotherapy (IOERT), delivered using a mobile linear accelerator, for the treatment of early breast cancer as an anticipated boost. Materials and methods A multidisciplinary Working Group, including several different professional profiles, was created before the beginning of clinical practice in 2012, with the purpose of writing the Flow Chart and applying the FMECA methodology to IOERT procedure. Several criticalities were identified a priori in the different steps of the procedure and a list of all potential failure modes (FMs) was drafted and ranked using the risk priority number (RPN) scoring system, based on the product of three parameters: severity, occurrence, and detectability (score between 1 and 5). The actions aimed at reducing the risk were then defined by the Working Group and the risk analysis was repeated in 2014 and in 2016, in order to assess the improvement achieved. Results Fifty-one FMs were identified, which represented the issues prospectively investigated according to the FMECA methodology. Considering a set threshold of 30, the evaluated RPNs show that 33 out of 51 FMs are critical; 6 are included in the moderate risk class (RPN: 31–40); 16 in the intermediate risk class (RPN: 41–50), and 11 in the high risk class (RPN: >50). Discussion The most critical steps concerned the surgical procedure and IOERT set-up. The introduction of the corrective actions into the clinical practice achieved the reduction of the RPNs in the re-analysis of the FMECA worksheet after 2 and 4 years, respectively. Conclusion FMECA proved to be a useful tool for prospective evaluation of potential failures in IOERT and contributed to optimize patient safety and to improve risk management culture among all the professionals of the Working Group.

Breastfeeding: a reproductive factor able to reduce the risk of luminal B breast cancer in premenopausal White women

In the medical literature, the role of breastfeeding and reproductive factors in the risk of breast carcinoma is still an open debate in premenopausal women. We highlight the role of breastfeeding and reproductive factors in luminal A and luminal B, the most frequent breast cancers. This case–control study analyzes a White premenopausal population of 286 breast cancer patients, divided into molecular subtypes, and 578 controls matched by age. Multivariate logistic regression models were used to assess the relationships of breastfeeding and other reproductive factors (age at menarche, parity, age at first pregnancy, number of children) with the risk of breast cancers. Among the variables examined, reproductive factors did not alter the risk of cancer, whereas breastfeeding up to 12 months was a significant protective factor against luminal B breast cancer (multivariate odds ratio: 0.22, 95% confidence interval: 0.09–0.59, P=0.002). In contrast, luminal A cases did not significantly correlate with breastfeeding or other reproductive factors. Breastfeeding up to 12 months is strongly protective against the more aggressive luminal B, but not against the less aggressive luminal A breast cancer in premenopausal White women.

Current Status of Fibroblast Growth Factor Receptor-Targeted Therapies in Breast Cancer

Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, metastatic breast cancer has a poor prognosis. In an era of personalized medicine, there is an urgent need for better knowledge of the biology leading to the disease, which can lead to the design of increasingly accurate drugs against patients’ specific molecular aberrations. Among one of the actionable targets is the fibroblast growth factor receptor (FGFR) pathway, triggered by specific ligands. The Fibroblast Growth Factor Receptors/Fibroblast Growth Factors (FGFRs/FGFs) axis offers interesting molecular targets to be pursued in clinical development. This mini-review will focus on the current knowledge of FGFR mutations, which lead to tumor formation and summarizes the state-of-the-art therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC.